Kose, Duygu; Un, Harun; Ugan, Rustem Anil; Halici, Zekai; Cadirci, Elif; Tastan, Tugba Bal; Kahramanlar, Aysenur

Objectives: We investigated, the effects of aprepitant (APRE) on the lung tissues of rats with an experimental polymicrobial sepsis model (CLP: Cecal ligation and puncture) biochemically, molecularly and histopathologically. Methods: A total of 40 rats were divided into 5 groups with 8 animals in each group. Group 1 (SHAM), control group; Group 2 (CLP), cecal ligation and puncture; Group 3 (CLP + APRE10), rats were administered CLP + 10 mg/kg aprepitant; Group 4 (CLP + APRE20), rats were administered CLP + 20 mg/kg aprepitant; and Group 5 (CLP + APRE40), rats were administered CLP + 40 mg/kg aprepitant. A polymicrobial sepsis model was induced with CLP. After 16 h, lung tissues were taken for examination. Tumour necrosis factor α (TNF-α) and nuclear factor-kappa b (NFK-b) messenger ribonucleic acid (mRNA) expressions were analysed by real-time PCR (RT-PCR), biochemically antioxidant parameters such as superoxide dismutase (SOD) and glutathione (GSH) and oxidant parameters such as malondialdehyde (MDA) and lung damage histopathologically. Key findings and conclusions: The GSH level and SOD activity increased while the MDA level and the expressions of TNF-α and NFK-b were reduced in the groups treated with APRE, especially in the CLP + APRE40 group. The histopathology results supported the molecular and biochemical results.

Türkeş, Cüneyt

Objectives: Proton-pump inhibitors (PPIs) are drugs commonly utilized by about 7% of adults in the world. Recent researches have shown that there are countless and severe side effects of these drugs. This situation has raised concern among clinicians and patients alike. The purpose of this study is to contribute the novel drug discovery and development technology and toxicology field by researching interactions of PPIs on paraoxonase 1. Methods: In this study, the paraoxonase 1 enzyme was purified from human serum by using rapid and straightforward chromatographic techniques. Subsequently, the inhibition effects of pantoprazole, omeprazole, and esomeprazole, PPIs, were investigated on paraoxonase 1. Besides, molecular docking studies were performed to unravel the binding mechanism between the enzyme and drugs. Key findings: All drugs showed potent inhibitory activities. IC50 of the drugs values were 54.780 ± 0.524, 86.470 ± 0.818 and 93.390 ± 0.885 mm and Ki constants were found as 39.895 ± 0.005 mm, 70.112 ± 0.010 mm and 78.868 ± 0.008 mm, respectively. The binding scores observed in silico studies were found to agree with the obtained from in-vitro experimental results. Conclusions: We observed that the drugs decreased PON1 activity at low concentrations. The results show that adjusting the dosages of these medications is a crucial case for each patient. The physicians should more carefully interpret whether there is an essential indication before prescribing PPIs and, if there is, to approve the proper dosing for the situation.